: The proposed study will address two areas of research which are important in understanding the etiology of cancers in finfish and shellfish. The first objective is the investigation of the role of the immune system in the initiation and progression of tumor in these animals. The second is the development and use of in vitro techniques to monitor neoplastic transformation in a specific class of cells, those derived from the embryonic neural crest, that are involved in a wide variety of tumors in fishes. The proposed studies will be based on a unique model system, damselfish neurofibromatosis (DNF), a malignant, transmissible cancer involving tumors in tissues derived from the embryonic neural crest, including neurofibromas, schwannomas and chromatophoromas. The histopathology, epizootiology and etiology of DNA are currently being investigated by this laboratory. Model systems of peripheral nerve sheath tumors (such as neurofibromas and schwannomas) using fishes are of special interest because mammalian models of these tumors are rare. The use of cultures of these cell types for the study of neoplastic transformation leading to such cancers has not been adequately explored in fishes or in mammals. Proposed studies include: 1) quantification of morphological, ultrastructural and antigenic differences in vitro between neoplastic cells from fish with DNA and their normal counterparts, 2) evaluation of alterations in cell surface receptors associated with pigment migration in chromatophores in DNF, 3) development of models of transformation based on the exposure of selected neuroectodermal cell types to transmissible factors isolated from tumors as well as selected chemical carcinogens. Preliminary studies have indicated that profound changes in immune function are associated with the progression of this disease and that an inflammatory infiltrate is characteristic of both spontaneous and experimentally induced tumors. Studies of the immunology of DNF will include: 1) an evaluation of changes in several cellular and humoral immune responses as the disease progresses, 2) measurement of effects of immunosuppression on latency, growth rate and histological features of experimentally induced tumors, 3) characterization of the structural, histochemical and functional cell types composing populations of tumor infiltrating leukocytes.